Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in ... [more ▼]

Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in vitro. Here we study the neurite outgrowth promoting effect of alpha-MSH on corticospinal (CS) neurons in vitro. Corticospinal neurons were identified in cell culture of neonatal rat cortex by immunostaining of cholera toxin subunit B (CTB), retrogradely transported from the cervical parts of the spinal cord. The CTB-immunoreactive neurons represent a small percentage (3-5%) of the total cell population after 72 h in vitro. The axons or dendrites of cortical and CTB-labelled layer V neurons were visualized using antibodies against axon- or dendrite-specific markers and measured using a semi-automatic quantification device. Here we report that alpha-MSH stimulates axonal as well as dendrite outgrowth from both total and CTB-labelled neurons with a bell-shape response curve. Axonal outgrowth of CTB-labelled neurons was dose-dependently stimulated with a maximal effect of 50% at 10(-10) M alpha-MSH. The maximal effect for stimulation of axon outgrowth for the total cortex population was observed at 10(-8) M alpha-MSH. In addition dendrite outgrowth of both total and CTB-labelled neurons is stimulated in a dose-dependent manner with maximal effects (varying between 46 and 48%) at 10(-8) M alpha-MSH. Explanations in the shift for the optimal alpha-MSH concentration for stimulation of axonal outgrowth of CTB-labelled layer V neurons as compared to total cortex neurons are discussed. [less ▲]

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an ... [more ▼]

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an original method consisting of the aggregation of calibrated poly-D,L-lactide microparticles. The size of the interstices between the aggregated microspheres was in a direct relationship to the microsphere diameter. A first approach was based on coating the microspheres with poly(vinyl alcohol) followed by chemically crosslinking the coating layers that were in mutual contact. This method was disregarded because of the acute cytotoxicity of glutaraldehyde used as the crosslinking agent, the absence of macroporosity, and the complete lack of flexibility. A physical technique of aggregation was then tested, which relied on the plasticization of poly-D,L-lactide microspheres with triethylcitrate to the point where microspheres strongly adhered to each other when they were in contact. This method has proved to be straightforward and definitely superior to the chemical approach, particularly with respect to cytotoxicity, control of macroporosity, and flexibility. A polymer support was thus successfully which was biodegradable, macroporous( interconnected pores of 10-100 microns in diameter), and flexible. This potential medical device is presently being used for neuronal transplantation in the central nervous system. [less ▲]